The Candidate: Dr. Bevin Zimmerman, a licensed veterinarian, is currently enrolled in a veterinary pathology training program and Ph.D. in the Department of Veterinary Biosciences and the Center for Retroviral Research at The Ohio State University (OSU), This K01 SERCA will support three years of her doctoral research (Phase I) and two years of post doctoral training (Phase II). The Environment: Dr. Zimmerman's sponsor, Dr. Michael Lairmore is Chair of the Department of Veterinary Biosciences with expertise in both veterinary pathology and retrovirology. Dr. Lairmore has extensive experience mentoring Ph.D. students and K award trainees. The Training Plan: This five year career development plan is divided into two phases. Phase I of the K award will allow Dr. Zimmerman to devote full time to research training that will culminate in her Ph.D. Phase II will promote Dr. Zimmerman's transition to an independent researcher. The Proposal: The research proposed in this application is focused on HTLV-1, the causative agent of Adult T cell Leukemia/Lymphoma (ATL) and Tropical Spastic Paraparesis (HAM/TSP). The virus is endemic in United States and is present worldwide. The goal of the research application is identify the unique cellular alterations that promote the resistance of ATL to conventional chemotherapy and exploit these cellular alteration using targeted molecules. The efficacy of the targeted therapies will be evaluated both in vitro and in a xenograft mouse model of ATL. Relevance to Public Health: There are currently 20-30 million people infected with HTLV-1 worldwide. Five percent of these people will develop Adult T cell Leukemia. The prognosis for ATL is poor and the median survival time, despite current therapies in less than one year. Our overall goal is identify therapies that may abrogate the resistance to therapy and thus, may eventually prolong survival.